Mutation screening of the PTEN gene in patients with autism spectrum disorders and macrocephaly.

• Mutations in the PTEN gene are associated with a broad spectrum of disorders, including Cowden syndrome (CS), Bannayan-Riley-Ruvalcaba syndrome, Proteus syndrome, and Lhermitte-Duclos disease. In addition, PTEN mutations have been described in a few patients with autism spectrum disorders (ASDs) and macrocephaly. In this study, we screened the PTEN gene for mutations and deletions in 88 patients with ASDs and macrocephaly (defined as >or=2 SD above the mean). Mutation analysis was performed by direct sequencing of all exons and flanking regions, as well as the promoter region. Dosage analysis of PTEN was carried out using multiplex ligation-dependent probe amplification (MLPA). No partial or whole gene deletions were observed. We identified a de novo missense mutation (D326N) in a highly conserved amino acid in a 5-year-old boy with autism, mental retardation, language delay, extreme macrocephaly (+9.6 SD) and polydactyly of both feet. Polydactyly has previously been described in two patients with Lhermitte-Duclos disease and CS and is thus likely to be a rare sign of PTEN mutations. Our findings suggest that PTEN mutations are a relatively infrequent cause of ASDs with macrocephaly. Screening of PTEN mutations is warranted in patients with autism and pronounced macrocephaly, even in the absence of other features of PTEN-related tumor syndromes.

Ämnesord

MEDICIN OCH HÄLSOVETENSKAP  -- Klinisk medicin -- Psykiatri (hsv//swe)

MEDICAL AND HEALTH SCIENCES  -- Clinical Medicine -- Psychiatry (hsv//eng)

Nyckelord

Abnormalities

Multiple

Genetics

Adolescent

Adult

Amino Acid Sequence

Asparagine

Genetics

Aspartic Acid

Genetics

Autistic Disorder

Complications

Genetics

Child

Child

Preschool

Craniofacial Abnormalities

Complications

Genetics

DNA Mutational Analysis

Exons

Genetics

Female

Genetic Testing

Humans

Introns

Genetics

Male

Molecular Sequence Data

Mutation

Genetics

PTEN Phosphohydrolase

Chemistry

Genetics

Syndrome

Publikations- och innehållstyp

ref (ämneskategori)

art (ämneskategori)